Various immunostimulators were examined in the strain 2 guinea pig L2C lymphoblastic leukemia model to determine their ability to therapeutically modulate the immune response of the host for the control of leukemic cell proliferation. The dose, route and frequency of administration of the stimulators alone and in conjunction with irradiated syngeneic blast cells was also evaluated as a function of time to obtain the optimal anti-leukemic effect. The combination of either BCG or C. parvum with irradiated blast cells 10 days following cytoreductive therapy with cytoxan at a time when the animals were in remission proved most effective in promoting long-term remissions beyond control values and allowed for a small percentage of cures. Additional forms of successful immunotherapy included the adoptive transfer of syngeneic, allogeneic and F1 hybrid cells specifically sensitized to the L2C leukemia following a reduction in the tumor load with chemotherapy. The effect of suppressor cells on the tumor-host relationship (e.g., ability of suppressor cells to inhibit tumor growth) has been established using a rat mammary carcinoma as a tumor model. Soluble serum factors controlling the regulation of the immune response are under investigation.